Risk assessment in pulmonary arterial hypertension (PAH): Insights from the GRIPHON study

The 2015 ESC/ERS guidelines propose a risk assessment strategy for PAH patients. Several recent registry analyses support the association between risk profile and survival in PAH. The present post-hoc analysis assessed the prognostic and predictive value of risk assessment in the context of the GRIPHON study, hitherto the largest randomized clinical trial in PAH. GRIPHON randomized 1156 PAH patients (predominantly pre-treated) to selexipag, a prostacyclin receptor agonist, or placebo. Analyses were performed on the composite primary endpoint (morbidity/mortality events) by number of low-risk criteria (WHO functional class I – II; 6-min walk distance > 440 m; NT-proBNP < 300 ng/L) at baseline and week 26. The number of low-risk criteria met at both baseline and week 26 was prognostic for outcome (P < 0.0001). The Kaplan-Meier estimates at year one for time to first morbidity/mortality event were 60.0% (95% CI: 54.9, 64.6), 83.4% (79.2, 86.8), 92.2% (87.9, 95.0), and 91.4% (75.7, 97.2) for patients with 0, 1, 2 and 3 low-risk criteria at baseline, respectively. The treatment effect of selexipag vs. placebo was consistent across the baseline risk subgroups (interaction P-value = 0.89). However, the corresponding analysis using the week 26 risk subgroups indicated that treatment response may increase with the number of low-risk criteria met at week 26 (interaction P-value = 0.052). Patients on selexipag were 1.69 times more likely to increase the number of low-risk criteria from baseline to week 26 vs. placebo (P = 0.002). These results support the association of a low-risk profile with improved long-term outcome, and suggest that selexipag treatment may improve the risk profile in patients with PAH.